Biomaterials made from polymers are being extensively applied in medicine and biotechnology, as well as in other industries. Applications include use as supporting materials, drug-delivery systems with different routes of administration and design, carriers of immobilized enzymes and cells, and materials for orthopedic applications.
Hyaluronic acid (HA) is a naturally occurring biopolymer, which serves important biological functions in bacteria and higher animals including humans. Naturally occurring HA may be found in the tissue of higher animals, in particular as intercellular space filler. It is found in greatest concentrations in the vitreous humour of the eye and in the synovial fluid of articular joints. In gram positive streptococci it appears as a mucoid capsule surrounding the bacterium.
Hyaluronic acid (HA) is a linear polysaccharide consisting of alternating units of β-1,4-D-glucoronic acid and β-1,3-N-acetyl-D-glucosamine. More particularly, HA is comprised of linear, unbranching, polyanionic disaccharide units consisting of glucuronic acid (GlcUA) an N-acetyl glucosamine (GlcNAc) joined alternately by beta 1-3 and beta 1-4 glycosidic bonds. It is a member of the glycosaminoglycan family which includes chondroitin sulphate, dermatin sulphate and heparin sulphate. Unlike other members of this family, it is not found covalently bound to proteins. Chemically, it is a nonsulfated glycosaminoglycan and occurs primarily in vivo as sodium hyaluronat. It is one of the major components of the extracellular matrix of connective tissues. It is present in synovial fluid of joints, in the vitreous body, in umbilical cord and in scaffolding that comprises cartilage. It plays an important role in many biological processes such as in tissue hydratation, in organization of the extracellular matrix, in lubrication and wound healing.
Hyaluronic acid is native to the body, it is a non-immunogenic, biocompatible, biodegradable and bioactive polysaccharide could be an ideal biomaterial for several biomedical applications, such as tissue engineering, drug- or gene-delivery systems. HA is soluble in water independently on its molecular weight, which typically ranged from 1×104 to 2×107 Da. The high molecular mass of HA indicated, that several depolymerization method have been developed, such as ultrasonic-, oxidative degradation, or acid hydrolysis, for preparing low molecular weight or oligomer HA.
Various methods have been developed for the cross-linking modification of hyaluronic acid, which commonly result in gel or film formation. In the type of covalently cross-linking reactions, cross-linkers are molecules with at least two reactive functional groups that allow the formation of bridges between polymeric chains. The most common cross-linkers of HA are aldehydes, thiols, hydrazides and other agents. Ionic cross-linking reactions with charged ions or molecules have also been employed by using several methods to form hydrogels, films or interpenetrating networks based on hyaluronic acid. Hydrogels have been utilized in a wide range of biomedical application, such as, scaffolds and carriers for drugs and gene, or implants for tissue engineering.
Many recent attempts have been made to create particulate systems based on polysaccharides. Hyaluronan nano- and Microsystems can be prepared in a wide range of methods. The emulsion cross-linking method and the coacervation are performed in emulsion. These processes avoid the use of toxic organic materials as cross-linking agents. The solvent evaporation method can be performed in a w/o emulsion also and the aqueous phase is removed by evaporation at high temperature. Spray-drying is a well-known technique to produce cross-linked suspension. This method is based on drying of finely dispersed droplets of solution in a stream of hot air followed by the addition of a cross-linking agent.
Hyaluronic acid is of increasing interest in drug delivery. It is known, for example, to enhance transport of hydrophilic drugs. It has also reported to be useful in colon- or nasal delivery. Hyaluronic acid is also of current interest as a carrier in gene delivery.